What is the recommended dosage and usage of Mounjaro (tirzepatide) for patients with type 2 diabetes?

Mounjaro (Tirzepatide) Dosing for Type 2 Diabetes

Start tirzepatide at 2.5 mg subcutaneously once weekly, then escalate by 2.5 mg every 4 weeks until reaching the target maintenance dose of 5 mg, 10 mg, or 15 mg weekly based on glycemic response and tolerability. 1, 2

Dosing Algorithm

Initiation and Titration:

• Begin at 2.5 mg subcutaneously once weekly 2
• Increase by 2.5 mg increments every 4 weeks 2
• Target maintenance doses: 5 mg, 10 mg, or 15 mg weekly 1, 3
• The dose escalation schedule allows for gastrointestinal tolerability while optimizing glycemic control 1

Maintenance Dosing:

• 5 mg weekly: Achieves HbA1c reduction of approximately 2.11% and weight loss of 5.4 kg 2
• 10 mg weekly: Achieves HbA1c reduction of approximately 2.40% and weight loss of 7.5 kg 2
• 15 mg weekly: Achieves HbA1c reduction of approximately 2.34% and weight loss of 8.8 kg 2
• Higher doses provide incrementally greater glycemic control and weight reduction, with 85-90% of patients achieving HbA1c <7% across all doses 2

Special Population Considerations

Renal Impairment:

• No dosage adjustment required for patients with eGFR ≥20 mL/min/1.73 m² 4
• Can be safely used across the spectrum of renal function without modification 4

Combination Therapy:

• Effective as monotherapy or combined with metformin for enhanced glycemic control 4, 1
• When added to titrated insulin glargine (with or without metformin), provides superior HbA1c reduction compared to insulin intensification alone 2
• Low risk of hypoglycemia when used without insulin or insulin secretagogues 3

Monitoring Requirements

Glycemic Monitoring:

• Track HbA1c regularly to assess glycemic response 4
• Monitor fasting and postprandial glucose levels 5
• Expect 23-62% of patients to achieve normoglycemia (HbA1c <5.7%) depending on dose 6

Weight Monitoring:

• Anticipate significant weight reduction of 6.2-12.9 kg depending on dose 3
• Expect 20.7-68.4% of patients to lose >10% of baseline body weight 6

Cardiovascular Parameters:

• Monitor blood pressure, as reductions are expected 3
• Track lipid profiles, particularly triglycerides which decrease with treatment 3

Perioperative Management

Elective Procedures:

• Hold tirzepatide the week before elective surgery due to delayed gastric emptying concerns 4
• This recommendation applies to all weekly GLP-1 receptor agonists and dual agonists 4

Cardiovascular Benefits

High-Risk Patients:

• Particularly beneficial for patients with established cardiovascular disease or elevated cardiovascular risk 4
• Meta-analysis across clinical trials showed no MACE hazard ratio >1.0, with upper confidence interval bounds <1.3, demonstrating cardiovascular safety 6
• MACE-4 events (nonfatal MI, nonfatal stroke, cardiovascular death, hospital admission for angina) tended to be reduced over 2-year periods 6

Safety Profile and Adverse Events

Common Side Effects:

• Gastrointestinal events are most frequent: nausea (13-18%), diarrhea (12-21%), decreased appetite, and vomiting 1, 2
• These are typically mild to moderate in severity and consistent with GLP-1 receptor agonist class effects 1
• Higher doses associated with increased GI adverse events 6

Hypoglycemia Risk:

• Low risk when used without insulin or insulin secretagogues 1, 3
• No increased risk of clinically significant or severe hypoglycemia in monotherapy or combination with metformin 1

Clinical Pitfalls to Avoid

• Do not skip the titration schedule: Rapid dose escalation increases gastrointestinal intolerance and discontinuation rates (18% at 15 mg vs 3% placebo when titration not followed properly) 2
• Do not use in decompensated cirrhosis: While tirzepatide reduces hepatic steatosis, safety data in decompensated liver disease is lacking 7
• Do not forget perioperative holds: Failure to discontinue before elective procedures may increase aspiration risk 4